The project is aimed at examining the delayed closure of the ductus arteriosus in the preterm infant by evaluating the relative role of the maturation of the contractile response of the vessel to agents like oxygen and comparing it with the role of agents that relax the vessel. This will be approached by: (1) evaluating whether the age dependent increases in responsiveness to contractile agents reflect a change in receptor function or contractile apparatus of the developing fetal vessel (examining the changes in response to contractile agonists on the content of cyclic nucleotides (cAMP and cGMP) in the tissue); (2) evaluating whether there is a significant lack of responsiveness in the immature ductus arteriosus to increasing PO2 by examining contractile responses of vessels from midgestation and term sheep fetuses in in vitro muscle tension baths; (3) evaluating whether the lamb ductus arteriosus is as sensitive to the relaxant effects of prostaglandin E1 in the high PO2 of postnatal existence as it is in the low PO2 of fetal existence by the use of in vitro muscle tension baths; (4) evaluating whether the different prostaglandins E1, E2, A2, F2-alpha and their major pulmonary metabolites will affect the contractile state of the lamb ductus arteriosus in vitro; and, (5) evaluating whether the fetal lamb lung at different gestational ages and in different states of inflation will metabolize prostaglandins differently by perfusing isolated lungs with radiolabelled prostaglandins and examining their effusates on thin layer chromatography.